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Myocardial Infarction Features Found With Multiomic Molecular Map

NEW YORK – A team from Germany, Slovenia, the Netherlands, UK, and US turned to single-cell gene expression profiling and other omics approaches to put together a "molecular map" of myocardial infarction effects — work that is expected to improve investigators' understanding of the coronary heart condition.

With the help of spatial gene expression profiling, single-nucleus RNA sequencing, single-cell ATAC-seq chromatin accessibility analyses, and other approaches, the researchers analyzed up to 191,795 individual cells to follow cardiac remodeling processes in 31 samples from 24 individuals, including samples collected at a range of time points after acute myocardial infarction in a subset of the participants.

The team's findings, published in Nature on Wednesday, highlighted the cell composition, cell states, gene expression, signaling pathway, and regulatory features that shift during myocardial infarction and recovery from it.

The study's co-senior and co-corresponding authors Rafael Kramann and Julio Saez-Rodriguez and their colleagues called the resulting human myocardial infarction integrative molecular map "an essential reference for the field" and suggested that the resource "paves the way for advanced mechanistic and therapeutic studies of cardiac disease."

At the time of the work, Kramann was affiliated with RWTH Aachen University and Erasmus Medical Center, while Saez-Rodriguez was with Heidelberg University and Informatics for Life in Heidelberg.

Past studies have shown that post-myocardial infarction remodeling of cardiac tissue includes the recruitment of immune cells and inflammatory effects, the team explained, along with steps that ultimately remove necrotic tissue, promote new vasculature, and produce scar tissue in the damaged area.

"Understanding the exact cellular and molecular mechanisms of cardiac remodeling processes from the acute ischemic event to the chronic cardiac scar formation in their spatial context will be key to developing novel therapeutics," the authors explained.

With that in mind, the investigators turned to spatial transcriptomics and single-cell profiles from affected and control heart samples to identify cardiomyocyte, endothelial cell, myeloid cell, and fibroblast cell states linked to myocardial infarction, while tracing cell state, expression, gene regulatory network, and between-cell dynamics.

"Our results provide a comprehensive spatially resolved characterization of gene regulation of the human heart in homeostasis and after myocardial infarction," the authors reported.

The investigators are reportedly releasing a publicly available, interactive version of the myocardial infarction molecular map for analyses by other research teams.

The authors further noted that "[w]e believe that our data will facilitate the understanding of spatial gene expression and gene-regulatory networks within the human myocardium and will be a resource for future studies that aim to understand the function of distinct cardiac cell types in cardiac homeostasis and disease."